Des-Arg(9)-bradykinin metabolism in patients who presented hypersensitivity reactions during hemodialysis: role of serum ACE and aminopeptidase P

Bradykinin (BK) has been proposed as the principal mediator of hypersensiti vity reactions (HSR) in patients dialyzed using negatively charged membrane s and concomitantly treated with angiotensin-converting enzyme (ACE) inhibi tors. We investigated the metabolism of exogenous BK added to the sera of 1 3 patients dialyzed on an AN69 membrane with a history of HSR (HSR+ patient s) and 10 others who did not present such a reaction (HSR-patients) while d ialyzed under the same conditions. No significant difference in the t(1/2) of BK was found between the patient groups. However, the t(1/2) of generate d des-Arg(9)-BK was significantly increased (2.2-fold) in HSR+ patients com pared to HSR-subjects. Preincubation of the sera with an ACE inhibitor (ena laprilat) significantly increased the t(1/2) of both BK and des-Arg(9)-BK i n both groups. There was no significant difference between the groups with respect to the t(1/2) of BK, but there was a significantly greater increase (3.8-fold) in the t(1/2) of des-Arg(9)-BK in HSR+ patients compared to HSR -subject. The level of serum aminopeptidase P (APP) activity showed a signi ficant decrease in the HSR+ sera when compared to HSR-samples. In HSR-and H SR+ patients, a significant inverse relation (r(2) = 0.6271; P < 0.00005) c ould be calculated between APP activity and des-Arg(9)-BK t(1/2). In conclu sion, HSR in hemodialyzed patients who are concomitantly treated with a neg atively charged membrane and an ACE inhibitor can be considered as a multif actorial disease in that a decreased APP activity resulting in reduced degr adation of des-Arg(9)-BK may lead to the accumulation of this B-1 agonist t hat could be responsible, at least in part, for the signs and symptoms of H SR. (C) 1999 Elsevier Science Inc. All rights reserved.